Recent years have seen many new and exciting developments in the mechanisms involved in the biosynthesis, intracellular segregation and proleolytic processing of secretory proteins and their various precursor forms. A new class of precursors is presently emerging, the so-called pre-secretory proteins, which have assumed great significance in understanding how the vectorial discharge of the secretory product into rough microsomal cisternae occurs. The previously discovered pro-proteins, as exemplified by proinsulin, have also been found by now to occur very widely, including, in a rather heterogeneous group, the precursors of many peptide hormones, toxins, serum proteins, enzymes, viral proteins, egg proteins, neurosecretory peptides, and even of structural proteins such as collagen. The two groups of precursors, the pre- and pro-proteins, can be distinguished in terms of their structure, kinetic behavior and cleavage mechanisms. It is becoming clear that limited intracellular and extracellular cleavage of these precursors plays an important role not only in biosynthesis, segregation, and secretion, but also in the coordinated bio-assembly of more complex oligomeric protein structures such as connective tissue fibers, membrane protein ensembles, and viral envelopes.